Depression is a disease showing symptoms such as chronic depressed mood, disappearance of interest and delight, marked change in the body weight, insomnia or hypersomnia, mental decay, psychomotor agitation or retardation, feeling of worthlessness and guilty, decay of thought and concentration, and suicidal ideation, according to Diagnostic and Statistical Manual of Mental Disorders: DSM-4 by American Psychiatric Association.
In the clinical condition of depression, the monoamine hypothesis related with the decrease in the neural transmission of serotonin, noradrenaline, and dopamine is proposed. For serotonin, in a healthy subject, a sufficient amount of serotonin is released from the presynaptic nerve terminal to the synaptic cleft, and the serotonin receptor present in the postsynaptic nerve terminal receives the serotonin, whereby signal transduction is achieved, and the serotonin transporter removes excessive serotonin from the synaptic cleft, and serotonin is released again from the presynaptic nerve terminal to the synaptic cleft. In a patient with depression, it is considered that the amount of serotonin released from the presynaptic nerve terminal is insufficient, so that the postsynaptic nerve terminal cannot receive a sufficient amount of serotonin. More specifically, in a patient with depression, the serotonin amount in the synaptic cleft is likely deficient.
Based on the monoamine hypothesis, there are a diagnosis of depression using serotonin as the index, and antidepressants including a selective serotonin reuptake inhibitor such as sertraline (SSRI) as an active ingredient.
It has been reported that the expression of serotonin transporter in the central nervous system is related with the expression in platelets and leucocytes. Based on the fact that the serotonin transporter in platelets and leucocytes containing lymphocytes has many common properties with the serotonin transporter in the central serotonin nerves, the serotonin transporter in the platelets and leucocytes containing lymphocytes obtained from the peripheral blood is studied as a biological marker of depression. It has been also reported that the serotonin transporter in platelets has the same gene sequence with that revealed at the serotoninergic neuronal system. It has been also reported that the change in the expression of the serotonin transporter is related with the function in the central nervous system and psychiatric symptoms such as seasonal affective disorder. However, the mechanism supporting the relationship is still unknown.
In addition, many depression model animals are proposed for development of antidepressants for treating serotonin-related depression. These model animals show the depression-like behavior, which is disappeared by the administration of serotonin or the inhibition of serotonin reuptake from the synaptic cleft. Accordingly, the depression model animals are used for the screening of the candidates for antidepressants.